Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells.
Epidermal growth factor, and its human homologue urogastrone (EGF/URO), are secreted by the gut-associated salivary and Brunner's glands. Recombinant EGF/URO is a powerful stimulator of cell proliferation and differentiation in the rodent and neonatal human intestine. But EGF/URO is not absorbed from the adult gut and has no action when given through the gut lumen; thus the role of secreted EGF/URO is unknown. We now report that ulceration of the epithelium anywhere in the human gastrointestinal tract induces the development of a novel cell lineage from gastrointestinal stem cells. This lineage initially appears as a bud from the base of intestinal crypts, adjacent to the ulcer, and grows locally as a tubule, ramifying to form a new small gland, and ultimately emerges onto the mucosal surface. The lineage produces neutral mucin, shows a unique lectin-binding profile and immunophenotype, is nonproliferative, and contains and secretes abundant immunoreactive EGF/URO. We propose that all gastrointestinal stem cells can produce this cell lineage after mucosal ulceration, secreting EGF/URO to stimulate cell proliferation, regeneration and ulcer healing. This cell lineage is very commonly associated with gastrointestinal mucosal ulceration, and we conclude that a principal in vivo role for EGF/URO is to stimulate ulcer healing throughout the gut through induction of this cell lineage in the adjacent mucosa.
Wright
N A
NA
ICRF Laboratories, Lincoln's Inn Fields, London, UK.
Pike
C
C
Elia
G
G
D003424:Crohn Disease / Q000473:pathology / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D006651:Histocytochemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008679:Metaplasia; D009077:Mucins / Q000378:metabolism; D010437:Peptic Ulcer / Q000473:pathology / Q000503:physiopathology*
D009077:Mucins; D004815:Epidermal Growth Factor